Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells.

Sheng H, Shao J, Morrow JD, Beauchamp RD, DuBois RN
Cancer Res. 1998 58 (2): 362-6

PMID: 9443418

Previously, we have shown that forced expression of prostaglandin endoperoxide synthase-2 [also called cyclooxygenase (COX) 2] leads to inhibition of programmed cell death in intestinal epithelial cells. More recently, we have demonstrated that growth of human colonic cancer xenografts is inhibited by treatment with a highly selective COX-2 inhibitor in tumors that express COX-2 (HCA-7) but not in those that lack COX-2 expression (HCT-116). To explore the biochemical mechanisms involved in these effects, we have evaluated the role of COX-2-derived eicosanoid products on programmed cell death in human colon cancer cells. Here we report that PGE2 treatment of human colon cancer cells leads to increased clonogenicity of HCA-7, but not HCT-116 cells. Treatment with a highly selective COX-2 inhibitor (SC-58125) decreases colony formation in monolayer culture and this growth inhibition was reversed by treatment with PGE2. Additionally, PGE2 inhibits programmed cell death caused by SC-58125 and induces Bcl-2 expression, but did not affect Bcl-x or Bax expression in human colon cancer (HCA-7) cells. Therefore, decreased cell death caused by PGE2 would enhance the tumorigenic potential of intestinal epithelial cells. Thus, these results may help to explain a component of the mechanism by which COX inhibitors prevent colorectal cancer in humans.

MeSH Terms (22)

Animals Apoptosis Clone Cells Colonic Neoplasms Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors Dinoprostone Dose-Response Relationship, Drug Humans Immunoblotting Isoenzymes Membrane Proteins Mice Mice, Nude Neoplasms, Experimental Prostaglandin-Endoperoxide Synthases Proto-Oncogene Proteins c-bcl-2 Pyrazoles Stem Cells Transplantation, Heterologous Tumor Cells, Cultured

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